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Abstract Objective This study focused on the investigation of the correlation between dietary retinol intake and rheumatoid arthritis (RA) using the National Health and Nutrition Examination Survey (NHANES) database. Methods Data from five NHANES cycles from 2003 to 2012 were utilized for this study. Dietary retinol intake was considered as the independent variable, and RA was the dependent variable. A weighted logistic regression method was applied to construct the relational model of the two variables. Stratified analysis without adjusting for confounding factors and subgroup analysis with confounding factors adjusted were conducted to explore the association between dietary retinol intake and RA. The optimal intake of dietary retinol was determined by the restricted cubic splines (RCS) analysis. Results 22,971 samples were included in this study. The weighted logistic regression model was employed to construct the relational model of dietary retinol intake and RA (OR: 0.95, 95% CI: 0.91–0.99, p = 0.019). Stratified analysis displayed a great influence on the relational model exerted by the interaction between gender and retinol intake (p for interaction = 0.014). A significant association between retinol intake and RA was also indicated in the model adjusted for demographic characteristics (OR: 0.95, 95% CI: 0.90-1.00, p = 0.029). Subgroup analysis by gender showed that in the female population, unadjusted model (OR: 0.90, 95% CI: 0.84–0.96, p = 0.002), model adjusted for demographic characteristics only (OR: 0.89, 95% CI: 0.83–0.96, p = 0.002), and model adjusted for all confounding factors (OR: 0.91, 95% CI: 0.85–0.99, p = 0.019) indicated dietary retinol intake as a protective factor against RA. RCS analysis demonstrated that in the female population, regardless of the model used (Crude, Model I, and Model II), an intake of dietary retinol > 354.86 mcg was associated with RA disease reduction (OR 354.86 mcg) to reduce the risk of RA.

Abstract Background Little has been done to establish biobanks for studying the environment and lifestyle risk factors for diseases among the school-age children. The Minhang Pediatric Biobank (MPB) cohort study aims to identify factors associated with health and diseases of school-aged children living in the urban or suburban area of Shanghai. Methods This population-based cohort study was started in all sub-districts/towns of Minhang district of Shanghai in 2014. First-grade students in elementary school were enrolled during the time of their routine physical examinations, with self-administered questionnaires completed by their primary caregivers. Additional information was extracted from multiple health information systems. Urine and saliva samples were collected during the baseline survey and follow-up visits. Results At the end of 2014 academic year, a total number of 8412 children and their parents were recruited, including 4339 boys and 4073 girls. All the participants completed the baseline survey and physical examination, and 7128 urine and 2767 saliva samples were collected. The five most prevalent childhood diseases in this population were dental caries, bronchitis, pneumonia, asthma and overweight/obese. Conclusions The MPB cohort has been successfully established, serving as a useful platform for future research relating to the genetic, environmental and lifestyle risk factors for childhood diseases.

The aging process profoundly impacts the systemic milieu, with specific blood-borne factors playing critical roles in its regulation. Platelet Factor 4 (PF4), released by platelets, has emerged as a novel blood-borne factor that contributes to the rejuvenation of aging brains in rodents. However, the age-related disparity in PF4 levels in humans remains poorly understood. To explore the relationship between PF4 and the natural aging process in humans, we collected peripheral blood (PB) samples from young (23.40 ± 2.13 years, n = 15) and elderly (75.23 ± 4.19 years, n = 13) individuals, along with cord blood (CB) samples (n = 15). ELISA analysis revealed higher PF4 levels in platelet-rich plasma lysate from young PB compared with that from elderly PB. Consistent with this, qPCR results demonstrated the highest PF4 expression in young PB among the three groups. In addition, FACS analysis showed increased expression of CXCR3 in mononuclear cells of young PB, indicating a greater responsiveness to PF4. Finally, our RNA-sequencing analysis corroborated platelets as a sensitive element during the natural aging process, and indicated platelets play a pivotal role in antioxidant response during aging, as evidenced by significant enrichment of several age-related pathways. These findings reveal that, alongside PF4 levels, platelets undergo substantial alterations during aging. Taken together, our data identified age-related disparities in platelets and PF4-related elements during natural aging and underscored the potential of targeting platelet modulation as an intervention in the aging process.

Knowledge of spring warm pool in the Bay of Bengal (BoBWP) is key for further understanding the climate variability in this region and beyond, but little is known about the BoBWP climatological state and the related mechanisms. In this study, we investigate the spatial structure and evolution of the BoBWP using daily Optimum Interpolation SST data from 1982-2022 in combination with multi-source data. Our analysis shows that the BoBWP is located in the central bay (6°-13°N) with a thickness around 20 m ~ 40 m. Composite analysis indicates that the BoBWP emerges in early April, peaks in early May and dissipates in early June. During the developing period, the net heat flux dominates the formation of spring warm pool through significant air-sea coupling processes, and induces the warming rate of 0.27°C/10d in the mixed layer, which is far larger than the contribution of oceanic dynamical processes (0.01°C/10d). During the decaying period, the net heat flux also plays a dominant role, with a cooling rate of -0.21°C/10d, meanwhile ocean dynamical processes contribute to the cooling of the warm pool with a rate of -0.01°C/10d. Additionally, the SST and the area of the BoBWP are significantly correlated with ENSO (r=0.66 and 0.73, p=0.05). During El Niño decaying year, the BoBWP primarily expands in a southward direction, with a 75% increase in area. Conversely, during La Niña decaying year, the BoBWP almost disappears, with a 52% decrease.

Abstract The Arabian Sea (AS) hosts the world's thickest and most intense oxygen minimum zone (OMZ), and previous studies have documented a dramatic decline of dissolved oxygen (DO) in the northeastern AS in recent decades. In this study, using the recently released data from Biogeochemical‐Argo floats, we found a surprising trend of recovery in deoxygenation within the core region of the OMZ in the AS (ASOMZ) since 2013. The average DO concentration increased by approximately threefold, from ∼0.63 μM in 2013 to ∼1.68 μM in 2022, and the thickness of the ASOMZ decreased by 13%. We find that the weakening of Oman upwelling resulting from the weakening of the summer monsoon is the main driver of oxygenation in the ASOMZ. In addition, the reduction of primary production linked to warming‐driven stratification reinforces deoxygenation recovery at depth.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

Abstract Background Resilience is crucial for older adults who experience adversities, but research on the issue in rural China remains limited. This study aims to examine factors associated with resilience among older adults in rural China, as related to different types of resilience, and under different levels of adversity. Methods Data were taken from the eight-wave (2001–2021) Longitudinal Study of Older Adults in Anhui Province, China. We used data from the eighth wave (2021) for the outcome variables and lagged predictors (2018) to avoid reverse causal effects. The study sample included individuals 60 years and above, excluding new participants from 2021, those without any adverse events, and any respondents with incomplete analytic data. Resilience was operationalized as residuals of the regressions of life satisfaction (Life Satisfaction Scale) and depressive symptoms (CES-D) on adversity, referred to as Type-1 and Type-2 resilience respectively. These two types of resilience were then treated as the outcome variables in subsequent multilevel regressions, with the predictors focusing on individual, social, and environmental characteristics and resources. This study adheres to STROBE guidelines. Results 43% of rural older adults exhibited both Type-1 and Type-2 resilience, whereas 18% exhibited only Type-1 resilience and 7% exhibited only Type-2 resilience. Common factors associated with both types of resilience included self-rated health, satisfaction with one’s own financial situation, and the prestigiousness of social networks. Predictors for higher levels of Type-1 resilience included higher levels of financial and emotional support and more options for places of leisure. Predictors for higher levels of Type-2 resilience included greater access to medical care. The prestigiousness of social networks, higher levels of emotional support and instrumental support, access to medical care, and more options of places of leisure were positively associated with resilience in the low-adversity group (first tertile of adversity), only satisfaction with financial situation was positively correlated with the resilience of the middle-adversity group (second tertile), while better self-rated health, satisfaction with financial situation, and financial support yielded greater resilience in the high-adversity group (third tertile). Conclusions We examined two types of resilience among older adults in rural China, and found that they have shared and unique associated factors. In addition, the potential factors influencing resilience varied with the level of adversity.

Strong salinity stratification induced by large freshwater fluxes in the northern Bay of Bengal (BOB) results in the formation of a quasi-permanent barrier layer (BL) that covers almost the entire BOB and leads to a unique temperature inversion within the thick BL in winter. In the presence of temperature inversions, the entrainment process at the bottom of the mixed layer (ML) induces warming effects in the ML, but little is known about this. In this paper, we quantify the contribution of the entrainment process to the ML temperature (MLT) in the northern BOB during the winter of 2013 using monthly and daily data from the Ocean General Circulation Model for the Earth Simulator version 2 (OFES2). It is found that the warming effect of the daily entrainment heat flux (EHF), which resolved the high-frequency variations, is 4 orders of magnitude larger than the monthly EHF for most of the wintertime. This significantly enhanced warming effect in daily data offsets up to 87% of the surface cooling induced by net heat flux during wintertime. A further analysis reveals that the larger daily EHF warming effect compared to its monthly counterpart is closely related to the deepened ML, the larger temperature difference within the ML and vertical velocity at the bottom of the ML.

Abstract Objective This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration. Methodology Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs. Results The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays. Conclusion The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.

Anthracyclines are the most fundamental and important treatment of several cancers especially for lymphoma and breast cancer. However, their use is limited by a dose-dependent cardiotoxicity which may emerge early at the initiation of anthracycline administration or several years after termination of the therapy. A full comprehending of the mechanisms of anthracycline-induced cardiotoxicity, which has not been achieved and is currently under the efforts, is critical to the advance of developing effective methods to protect against the cardiotoxicity, as well as to early detect and treat it. Therefore, we review the recent progress of the mechanism underlying anthracycline-induced cardiotoxicity, as well as approaches to monitor and prevent this issue.

Objective: Recently, liquid platelet-rich fibrin (PRF), a rich source of concentrated platelets and growth factors, has emerged as a promising agent for stimulating tissue regeneration. However, its specific efficacy in chondrocyte proliferation and cartilage regeneration remains underexplored. To address this question, we investigated liquid PRF obtained through horizontal centrifugation and compared its effects with hyaluronic acid (HA), a high molecular weight glucosamine supplement widely used in clinical practice to safeguard against chondral damage.Materials and Methods: Liquid PRF, produced using horizontal centrifugation (liquid H-PRF) at 500 g for 8 min, served as our experimental agent. We conducted cell viability and proliferation assays using PRF-conditioned medium. We assessed the chondrocyte phenotype of ATDC5 cells through toluidine blue and alcian blue staining, real-time polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence staining. Furthermore, we examined the expression of genes involved in inflammation through RT-PCR and Western blot analysis.Results: Liquid H-PRF exerted notable effects on chondrocytes, influencing proliferation, inflammatory responses, and chondrogenic differentiation. The H-PRF group displayed significantly higher expression of chondrogenic markers, including Col2a1, compared to HA-treated cells, whereas aggrecan expression was significantly higher in the HA group. PRF also demonstrated the ability to reduce inflammatory levels in chondrogenic ATDC5 cells, and this effect was further enhanced when PRF from the buffy coat zone was added. In comparison, chondrocytes cultured in the HA group produced significantly fewer inflammatory factors than those in the PRF group, as confirmed qualitatively by Western blot analysis.Conclusion: Liquid H-PRF emerged as a potent stimulator for chondrogenesis and a regulator of the inflammatory response, achieving levels similar to HA. Moreover, liquid H-PRF exhibited strong potential for enhancing the production of cartilage extracellular matrix and promoting chondrogenic regeneration with notably increased Col2a1 levels. Future research should encompass animal studies and human trials to further evaluate the comparative effectiveness of liquid PRF versus HA, potentially as an alternative or complementary strategy for future clinical applications.

In this study, we investigate the connection between planetary equatorial waves, modulated by the Indian Ocean dipole (IOD) and El Niño Southern Oscillation (ENSO), and the interannual variabilities of the salinity distribution in the Bay of Bengal (BoB) in October–December (OND), along with its associated dynamics, using satellite and reanalysis datasets. In OND 2010 and 2016 (1994, 1997, 2006, and 2019), positive (negative) sea surface salinity anomalies (SSSAs) were distributed in the eastern equatorial Indian Ocean (EIO) and Andaman Sea. Moreover, the southward movement of negative (positive) SSSAs along the eastern Indian coast was observed. This phenomenon was caused by large-scale anomalous currents associated with zonal wind over the EIO. During OND 2010 and 2016 (1994, 1997, 2006, and 2019), due to anomalous westerlies (easterlies) over the EIO and anomalous downwelling (upwelling) Kelvin waves, the strengthened (weakened) Wyrtki jet and the basin-scale anomalous cyclonic (anticyclonic) circulation in the BoB gave rise to positive (negative) SSSAs within the eastern EIO and Andaman Sea. In addition, the intensified (weakened) eastern Indian coastal currents led to the southward movement of negative (positive) SSSAs. It is worth noting that downwelling Kelvin waves reached the western coast of India during OND 2010 and 2016, while upwelling Kelvin waves were only confined to the eastern coast of India during OND 1994, 1997, 2006, and 2019. Furthermore, westward salinity signals associated with reflected westward Rossby waves could modulate the spatial pattern of salinity. The distribution of salinity anomalies could potentially influence the formation of the barrier layer, thereby impacting the sea surface temperature variability and local convection.

Background: The Rutgeerts score (RS) is widely used to predict postoperative recurrence after ileocolonic resection for Crohn’s disease (CD) based on the severity of lesions at the neoterminal ileum and anastomosis (RS i0–i4). However, the value of anastomotic ulcers remains controversial. Objectives: Our aim was to establish a nomogram model incorporating ileal and anastomotic lesions separately to predict the long-term outcomes of CD after ileal or ileocolonic resection. Design: A total of 136 patients with CD were included in this retrospective cohort study. Methods: Consecutive CD patients who underwent ileal or ileocolonic resections with postoperative ileocolonoscopy evaluation within 1 year after the surgery were included. The primary endpoint was postoperative clinical relapse (CR). An endoscopic classification separating ileal and anastomotic lesions was applied (Ix for neoterminal ileum lesions; Ax for anastomotic lesions). A nomogram was constructed to predict CR. The performance of the model was evaluated by the receiver-operating characteristic (ROC) curve and decision curve analysis (DCA). Results: CR was observed in 47.1% ( n = 64) of patients within a median follow-up of 26.9 (interquartile range, 11.4–55.2) months. The risk of CR was significantly higher in patients with an RS ⩾ i2 assessed by the first postoperative endoscopy compared with patients with an RS ⩽ i1 ( p

Abstract Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMβ, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases. Video abstract

ObjectivesThis study aimed to compare the burden and trends of stroke attributed to dietary risk factors in the Belt and Road (“B&R”) countries from 1990 to 2019.MethodsThe 2019 Global Burden of Disease (GBD) Study was used to gather information on the burden of stroke attributable to dietary risk factors. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) were determined in 1990 and 2019 among the “B&R” countries. The average annual percent change (AAPC) was used to analyze the temporal trends of diet-induced stroke DALYs from 1990 to 2019 and in the final decade (2010–2019) by Joinpoint regression analysis.ResultsIn 2019, the absolute number of stroke deaths and DALYs attributable to dietary risk factors were 671,872 cases (95% UI 436,354–937,093) and 1.67 million cases (95% UI 1.15–2.24) in China. We found geographical differences in mortality and DALYs of diet-attributable stroke among member countries, with Bulgaria, Hungary and Serbia being the three highest countries in 1990, Bulgaria, North Macedonia and Montenegro in Central Asia in 2019. The ASRs of diet-induced stroke mortality and DALYs were generally declining in most member states from 1990 to 2019, however, the corresponding metrics in Mongolia remained high. The fastest decline in ASR of mortality and DALYs for diet-induced stroke was seen in Estonia, Eastern Europe, with AAPC values of −7.09% (95%CI: −7.72, −6.46%) and − 6.62% (95%CI: −7.20, −6.03%), respectively. We noted a substantial downward trend in ASR of mortality and DALYs from diet-induced stroke changes in the final decade (2010–2019) for most member states. The ASR of DALYs for diet-induced stroke decreased greater in females than in males. For those aged 50–74, the DALYs for stroke due to dietary risk factors in all other member countries of the “B&R” showed a decreasing trend, except for the Philippines, which rose (AAPC = 2.13, 95%CI: 1.40–2.87%) and Turkmenistan, which remained stable (AAPC = 0.05, 95%CI: −0.43–0.33%).ConclusionThe burden of diet-induced stroke varies substantially across “B&R” countries and threaten public health, relevant evidence-based policies and interventions should be adopted to address the future burden of stroke in “B&R” countries through extensive collaboration.

Abstract Background In December 2019, many cases of COVID‐19 were reported in Wuhan City, Hubei Province, China. In the following 3 months, the disease out broke in China. Preisolation measures was used to screen out COVID‐19 patients in the pediatric respiratory ward of our hospital. Aims To investigate the new measures for screening COVID‐19 patients and to analyze the clinical features of children with suspicious COVID‐19. Methods A total of 50 preisolated children with suspicious COVID‐19 who were admitted to our hospital in Mianyang, China, between January 28 and March 5, 2020, were included. Patients presented with fever and cough or fever accompanied by vomiting and diarrhea. A detailed epidemiological history screening was performed. A real‐time reverse‐transcriptase–polymerase‐chain‐reaction (RT‐PCR) was used to detect SARS‐COV‐2 nucleic acid. Low‐dose chest computed tomography (CT) was applied when pneumonia was suspicious. Routine blood tests were performed to rule out COVID‐19. Patients' data were collected, and the basic clinical features, epidemiological history, clinical manifestations, auxiliary examination results, and outcomes were analyzed and summarized. Results No definite cases were detected, while two patients were suspected of having COVID‐19. The pathogenic results of the 50 patients mainly included Mycoplasma pneumoniae, followed by Epstein–Barr virus, and rotavirus. Thirty‐five patients suffered from bronchopneumonia. The preisolated patients had similar clinical and epidemiological characteristics as patients with fever, cough, vomiting, and diarrhea. Conclusions Preisolation measures combined with pathogen screening can minimize the risk of hospital‐acquired infections by preventing patients with suspicious COVID‐19 from contacting other patients before they are explicitly excluded. Clinical analysis of the patients was helpful for clinical nursing management.

Background: Transmural healing (TH) is a potential therapeutic goal of Crohn’s disease (CD) and is associated with better clinical outcomes. However, few studies have described early TH and its predictors. Objectives: We aimed to evaluate early TH and its predictors using magnetic resonance enterography (MRE) in patients with CD receiving ustekinumab (UST). Design: This was a retrospective observational study. Methods: Patients with active CD treated with UST and their intestinal segments with bowel wall thickness (BWT) ⩽ 3 mm at baseline were included. Clinical characteristics, laboratory indicators, endoscopic manifestations, and MRE indices were evaluated at baseline and week 26 (W26) of the therapy. The following MRE parameters were assessed: BWT, edema, apparent diffusion coefficient (ADC), Clermont score, Magnetic Resonance Index of Activity score, fat stranding, comb sign, and stricture. TH was defined as BWT ⩽ 3 mm without any signs of inflammation (i.e., ulceration, edema, diffusion-weighted hyperintensity, and increased contrast enhancement) at W26. Results: The study included 37 patients with 106 intestinal segments (including 15 proximal small intestines, 33 terminal ilea, and 58 colons). Clinical features, laboratory indicators, endoscopic results, and MRE parameters at W26 were significantly improved after UST treatment in both patient-based and intestinal segment-based analysis. Seven (18.9%) patients and 26 (24.5%) intestinal segments achieved TH at W26. Baseline BWT [odds ratio (OR) = 0.287, 95% confidence interval (CI), 0.090–0.918, p = 0.035] and ADC (OR = 2.997, 95% CI, 1.009–8.908, p = 0.048) predict TH of patients at W26. Baseline ADC (OR = 2.857, 95% CI, 1.285–6.349, p = 0.010) and presence of stenosis (OR = 0.196, 95% CI, 0.052–0.735, p = 0.016) were associated with TH of segments at W26. Conclusion: Early TH assessed by MRE was observed in nearly one-fifth of patients with CD and intestinal segments after UST treatment for 26 weeks. Baseline MRE indices such as BWT and presence of stenosis might negatively predict TH, while ADC might positively predict early TH.

An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.

Lake flow is one of the common hydrological phenomena in nature. The water exchange of lakes and the circulation of natural water resources are realized by the water movement caused by various factors. Lake current is of great significance in the hydrological and ecological environment and it is one of the focuses of scholars’ research. This paper takes Poyang Lake as the research area, and uses three texture enhancement methods of Laws, Gabor, and LBP operators to enhance the texture features of images based on multi-source remote sensing data, and uses the Hough transform to extract the flow direction of the Poyang Lake area. The results show that the three texture enhancement methods combined with Hough transform can extract the flow direction, but the Gabor filter has the best flow direction effect and the highest extraction accuracy. Gabor filter is the most adaptable for texture enhancement of images with different resolutions. HIGHLIGHTS This paper compared the adaptability of Laws, Gabor filtering and LBP algorithms to the images with different resolutions and different regions.; Hough transform was used to extract the water flow direction of Poyang Lake.; The seasonal flow direction of Poyang Lake was analyzed.;

Abstract This study explored the characteristics of marine heatwaves (MHWs) and the related dynamics in Bay of Bengal (BOB) associated with El Niño events during 1982–2020. This showed that El Niño can induce more MHW days, which displays remarkable seasonality. The strong influences of El Niño were found in the southern BOB at its peak phase in winter and the following spring, characterized by an increase in MHW days by 106% in winter and 83% in spring. In the proceeding summer, its influences weakened and shifted to the central bay. The more MHW days during winter and spring are primarily caused by the enhanced solar radiation associated with El Niño and partly contributed by the thick barrier layer in winter. In contrast, besides atmospheric heating, the deepening thermocline in the central bay induced by equatorial and local winds also plays an important role in the increase in MHWs during summer.

Androgen biosynthesis enzyme 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 has emerged as a potential driver for therapeutic resistance in prostate cancer. Patients with homozygous HSD3B1(1245C) inheritance are intrinsically more resistant to currently available androgen/androgen receptor–targeting (AR-targeting) drugs. In this issue of the JCI, Li et al. present data on the regulation of 3βHSD1 phosphorylation and activity by tyrosine kinase BMX. Inhibition of BMX activity by genetic or pharmacologic approaches blocked androgen biosynthesis in prostate cancer cells and inhibited tumor growth in preclinical xenograft models. The findings provide insights into mechanisms underlying castration resistance in prostate cancer and reveal a potential strategy to circumvent therapeutic resistance in patients with homozygous HSD3B1(1245C) inheritance.

We herein report the observation of a slope undercurrent beneath the winter western boundary current of the northwestern South China Sea (SCS), and its spatiotemporal variation. The possible underlying dynamics are also discussed. In situ observations reveal that the northeastward undercurrent is located above the upper slope with a core velocity exceeding 20 cm/s, which extends from 200 m to 800 m in depth with a width of 30–50 km and an along-slope length of approximately 200 km in deep winter of 2006-2007, and is characterized with interseasonal and interannual variabilities. The existence of this undercurrent is also supported by Hybrid Coordinate Ocean Model (HYCOM) results. We find that the slope undercurrent is probably driven by the along-slope pressure gradient associated with the sea level set-up off the continental slope of south Hainan Island and modulated by mesoscale eddies and Rossby waves. This study will renew our knowledge of the deep slope currents in the northwestern SCS.

Summary: Background: Social determinants of health (SDOH) produce a broad range of life expectancy (LE) disparities. In China, limited literatures were found to report association between SDOH and LE at ecological level during a consecutive period of time from the spatial perspectives. This study aimed to determine the existence, quantify the magnitude, and interpret the association between SDOH and LE in China. Methods: Provincial-level LE were estimated from mortality records during 2005–2020 from National Mortality Surveillance System in China. A spatial panel Durbin model was used to investigate LE associated SDOH proxies. Spatial spillover effects were introduced to interpret direct and indirect effects caused by SDOH during long-term and short-term period on LE disparities. Findings: Nationwide, LE increased from 73.1 (95% confidence interval (CI): 71.3, 74.4) years to 77.7 (95%CI: 76.5, 78.7) years from 2005 to 2020. Unequally spatial distribution of LE with High-High clustering in coastal areas and Low-Low clustering in western regions were observed. Locally, it was estimated that SDOH proxies statistically significant related to an increase of LE, including GDP (coefficient: 0.02, 95%CI: 0.00, 0.03), Gini index (coefficient: 2.35, 95%CI: 1.82, 2.88), number of beds in health care institutions (coefficient: 0.02, 95%CI: 0.00, 0.05) and natural growth rate of resident population (coefficient: 0.02, 95%CI: 0.01, 0.02). Direct and indirect effects decomposition during long-term and short-term of LE associated SDOH proxies demonstrated that GDP, urbanization rate, unemployment rate, education attainment, Gini index, number of beds in health care institutions, sex ratio, gross dependence ratio and natural growth rate of resident population not only affected local LE, but also exerted spatial spillover effects towards geographical neighbors. Interpretation: Spatial variations of LE existed at provincial-level in China. SDOH regarding socioeconomic development and equity, healthcare resources, as well as population characteristics not only affected LE disparities at local scale but also among nearby provinces. Externalities of policy of those SDOH proxies should be took into consideration to promote health equity nationally. Comprehensive approaches on the basis of population strategy should be consolidated to optimize supportive socioeconomic environment and narrow the regional gap to reduce health disparities and increase LE. Funding: National Key Research & Development Program of China (Grant No.2018YFC1315301); Ministry of Education of China Humanities and Social Science General Program (Grant No.18YJC790138).

Introduction/Aims: Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H2S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism. Methods: Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target ­protein after renal IRI. Results: The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1. Conclusions: GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.

BackgroundTelemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. ObjectiveThis systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. MethodsWe systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. ResultsA total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference −0.71, 95% CI −1.07 to −0.36; P

Infection is a growing issue in artificial implants and has become an area of significant interest. Here, the authors report on graphdiyne titanium dioxide composite nanofibres with enhanced photocatalytic reactive oxygen species generation and osteoinductive properties, demonstrated in infected implant models.

Abstract Background Epidemiological studies have suggested that adiponectin is associated with the development of insulin resistance and type 2 diabetes. This study first examined the effect of purified anthocyanins, a group of dietary flavonoids, on serum adiponectin in patients with prediabetes and newly diagnosed diabetes. Methods A total of 160 patients with prediabetes (n = 90) or newly diagnosed diabetes (n = 70) were randomly assigned to either the anthocyanins group or the placebo group for 12 weeks of intervention. Serum adiponectin, a set of biomarkers related to glucolipid metabolism, anthropometric parameters, dietary intake and physical activity were measured before and after intervention. Results Anthocyanins increased serum adiponectin compared with placebo (net change 0.46 µg/mL, 95% CI [0.03, 0.90], p = 0.038) in the subjects with newly diagnosed diabetes. No significant difference in the change in adiponectin was observed between the two groups either in the overall subjects (0.02 µg/mL [− 0.32, 0.36], p = 0.906) or in prediabetes (− 0.35 µg/mL [− 0.85, 0.16], p = 0.174). Anthocyanins also decreased fasting glucose (− 0.5 mmol/L [− 1, − 0.04], p = 0.035) in the subjects with newly diagnosed diabetes, but no such change was observed in those with prediabetes. Conclusions Anthocyanins supplementation for 12 weeks improved serum adiponectin and fasting glucose in patients with newly diagnosed diabetes, but not in patients with prediabetes. Trial registration ClinicalTrials.gov, NCT02689765. Registered on 6 February 2016, https://clinicaltrials.gov/ct2/show/NCT02689765 .

Abstract Background Hypertriglyceridemic waist (HTGW) phenotype has been suggested as a risk factor for chronic kidney disease (CKD). However, there is limited evidence on the relationship of triglyceride waist phenotypes with estimated glomerular filtration rate (eGFR) status and severity. Our aim was to explore the associations of triglyceride waist phenotypes with reduced eGFR and various decreased eGFR stages among Chinese adults. Methods A population-based, cross-sectional study was conducted among Chinese participants aged 20–74 years from June 2016 to December 2017 in Shanghai, China. An eGFR value below 60 mL/min/1.73 m2 was defined as decreased eGFR. HTGW phenotype was defined as triglyceride (TG) ≥1.7 mmol/L and a waist circumference (WC) of ≥90 cm for men and ≥ 80 cm for women. We examined the association of triglyceride waist phenotypes with decreased eGFR risk using the weighted logistic regression models. Results A total of 31,296 adults were included in this study. Compared with normal TG level/normal WC (NTNW) phenotype, normal TG level/enlarged WC (NTGW) and elevated TG level/enlarged WC (HTGW) phenotypes were associated with the increased risk of decreased eGFR. Multivariable-adjusted ORs (95% CI) associated with NTGW, elevated TG level/normal WC (HTNW), and HTGW phenotypes were 1.75 (1.41–2.18), 1.29 (0.99–1.68), and 1.99 (1.54–2.58), respectively. These associations between triglyceride waist phenotypes and decreased eGFR risk remained across almost all the subgroups, including sex, age, BMI, T2DM, and hypertension. HTGW phenotype was consistently positively associated with the risk of mildly and moderately decreased eGFR, but not with severely decreased eGFR risk. Conclusions HTGW was consistently associated with the increased risk of decreased eGFR and various decreased eGFR stages, except for severely decreased eGFR. Further prospective studies are warranted to confirm our findings and to investigate the underlying biological mechanisms.

Background/Aims Crohn’s disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population’s ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD. Methods This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay. Results The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, P

Based on Soil Moisture and Ocean Salinity (SMOS) data and the Ocean Reanalysis System 5 (ORAS5) dataset, positive salinity anomalies exceeding 2 psu in the northern Bay of Bengal (BoB) and negative salinity anomalies with the peak of the freshening anomalies reaching −2 psu around Sri Lanka were observed in autumn 2010. Here, an analysis of the anomalous salt budget revealed that anomalous horizontal advection contributed most to the variability in salinity in the BoB. With the development of La Niña and negative Indian Ocean dipole (nIOD) in summer and autumn, the strong summer monsoon current and Wyrtki jet combined with the anomalous basin-scale cyclonic circulation led to more high-salinity water entering the northern BoB. In addition, more freshwater was transported southward along the eastern coast of India by east Indian coastal current (EICC) in autumn, resulting in extremely negative salinity anomalies around Sri Lanka and positive salinity anomalies in the northern BoB. Moreover, the freshwater around Sri Lanka was carried farther into the southeastern Arabian Sea by the west Indian coastal current (WICC) in November, which affected the salinity stratification in winter and then influenced the variation of the Arabian Sea Mini Warm Pool (ASMWP) in the following spring. The ASMWP could affect the Indian summer monsoon (ISM) through its influence on the monsoon onset vortex (MOV) over the southeast Arabian Sea (SEAS).

The southern Bay of Bengal (BOB) cold pool (SCP) plays an important role in the regional climate fluctuation of the BOB. However, the interannual variability in the SCP is still unknown. Multisource satellite remote sensing data and assimilation have been applied to explore the interannual variability in the SCP and its relationship with El Niño–Southern Oscillation (ENSO) events for the period 1982–2020. The anomalous SST of the SCP in the summer following the peak phase (i.e., winter) of the ENSO was closely related to the ENSO events. El Niño (La Niña)-induced the warm (cold) anomaly of the SCP starting from May and persisted throughout August with a peak value appearing in June during the El Niño (La Niña) decaying years. In the El Niño decaying years, the southwest monsoon current (SMC) was weakened, forced locally by the weakening southwesterly wind and remotely by the easterly wind anomaly at the equator associated with El Niño. The El Niño-related weakening SMC and the associated less cold advection led to the warm anomaly of the SCP. In addition, El Niño-related atmospheric heating also made a comparable contribution to the evolution of the SCP’s SST. In the early stage (15 May to 10 June), its contribution to the warming of the SCP was much larger than that of the SMC, whereas from mid-June to August, it reversed to have a cooling effect and partially offset the advection heating induced by the SMC on the SCP. In the La Niña decaying years, similar oceanic and atmospheric processes operated but in an opposite way.

Objectives People who inject drugs (PWID) experience a high burden of injection drug use-related infectious disease and challenges in accessing adequate care. This study sought to identify programmes and services in Canada addressing the prevention and management of infectious disease in PWID.Design This study employed a systematic integrative review methodology. Electronic databases (PubMed, CINAHL and Web of Science Core Collection) and relevant websites were searched for literature published between 2008 and 2019 (last search date was 6 June 2019). Eligible articles and documents were required to address injection or intravenous drug use and health programmes or services relating to the prevention or management of infectious diseases in Canada.Results This study identified 1607 unique articles and 97 were included in this study. The health programmes and services identified included testing and management of HIV and hepatitis C virus (n=27), supervised injection facilities (n=19), medication treatment for opioid use disorder (n=12), integrated infectious disease and addiction programmes (n=10), needle exchange programmes (n=9), harm reduction strategies broadly (n=6), mobile care initiatives (n=5), peer-delivered services (n=3), management of IDU-related bacterial infections (n=2) and others (n=4). Key implications for policy, practice and future research were identified based on the results of the included studies, which include addressing individual and systemic factors that impede care, furthering evaluation of programmes and the need to provide comprehensive care to PWID, involving medical care, social support and harm reduction.Conclusions These results demonstrate the need for expanded services across a variety of settings and populations. Our study emphasises the importance of addressing social and structural factors that impede infectious disease care for PWID. Further research is needed to improve evaluation of health programmes and services and contextual factors surrounding accessing services or returning to care.PROSPERO registration number CRD42020142947.

With the development of telecom industry,growing web service operations need more people to maintain the quality of the service.In the branch of telecom operation service,installation and maintenance service,the service quality is evaluated by human through assessing picture of construction site.The traditional way of evaluating quality of operation service brings low accuracy and high labor cost.In recent years,image recognition technology developed well with the deep learning raised,the related application field were broaden.If image recognition techniques were applied in telecom operation and maintenance system,the labor cost would be saved and the recognition accuracy would be improved.Several image recognition techniques were applied in installation quality assessment of telecom operation and maintenance system,and the performance and accuracy were analyzed.Based on analysis,a combining image recognition model was further proposed.The image recognition accuracy and efficiency of quality assessment was improved.

Objectives: This study was undertaken to compare gut hormone secretion between high-fat-fed and control rats, and to examine the corresponding changes in the expression of sweet taste receptors and glucose transporters in the small intestine and hypothalamus. Methods: Four-week-old male Sprague Dawley rats were fed a standard or high-fat diet for 8 weeks (10 in each group), followed by an oral glucose tolerance test (50% glucose solution, 2 g/kg). Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) assays. One week later, small intestinal and hypothalamic tissue were analyzed for sweet taste receptor and glucose transporter expression by real-time PCR. Results: After oral glucose, plasma GLP-1 concentrations were higher in high-fat-fed than standard-fat-fed rats (group × time interaction, p < 0.01) with significant differences at t = 15 min (p < 0.01) and 30 min (p < 0.05). Plasma PYY concentrations were lower in high-fat-fed than control rats at t = 0, 15 min (p < 0.05, respectively) and 120 min (p < 0.01). There were no differences in the expression of sweet taste receptors or glucose transporters between high-fat-fed and control rats in the duodenum, ileum, or hypothalamus. Conclusions: Changes in GLP-1 and PYY secretion after a high-fat diet appear unrelated to any changes in the expression of sweet taste receptors or glucose transporters. Impaired PYY secretion with high-fat feeding suggests that PYY analogues may provide a potential therapy in the treatment of obesity.

Abstract Background The incidence of Ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. The aim of this study was to identify risk factors predictive of extent progression in Asian patients with UC and to evaluate the clinical outcome by longitudinal follow-up. Methods We retrospectively analyzed 518 UC patients without ascending colon involvement at diagnosis who were regularly followed and underwent colonoscopy between 2003 and 2016 in an Asian tertiary referral center. Proximal disease extension and associated risk factors were analyzed. Results A total of 91 (17.6%) patients experienced proximal disease extension followed for a median period of 7.5 years. The median time for extent extension was 16.1 months (interquartile range (IQR) 8.3–42.2). The cumulative rate of disease extension was 9.9, 14.9, 19.6, 24.6 and 30.5% at 1,2,3,4 and 5 years after diagnosis. 43 (12.0%) patients with E1/E2 progressed to E3, and 40 (21.9%) with E1 progressed to E2. Of patients diagnosed with E3 involvement limited to the hepatic flexure distally, 8 (13.3%) progressed to pancolitis. Cox regression analysis found that disease extent at diagnosis was the sole predictor of disease extension (odds ratio (OR),1.74, 95% confidence interval (CI) 1.18–2.57, p = 0.01). Proximal disease extension was associated with disease relapse (p = 0.03) and increased use of steroids and immunosuppressive agents (p

Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P < 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD.

Background: A suitable disease classification is essential for individualized therapy in patients with Crohn’s disease (CD). Although a potential mechanistic classification of colon-involving and non-colon-involving disease was suggested by recent genetic and microbiota studies, the clinical implication has seldom been investigated. We aimed to explore the association of this colonic-based classification with clinical outcomes in patients with CD compared with the Montreal classification. Methods: This was a retrospective study of CD patients from a tertiary referral center. Patients were categorized into colon-involving and non-colon-involving disease, and according to the Montreal classification. Clinico-demographic data, medications, and surgeries were compared between the two classifications. The primary outcome was the need for major abdominal surgery. Results: Of 934 patients, those with colonic involvement had an earlier median (interquartile range) age of onset [23.0 (17.0–30.0) versus 26.0 (19.0–35.0) years, p = 0.001], higher frequency of perianal lesions (31.2% versus 14.5%, p

As a major gaseous pollutant, ozone (O3) adversely affects human health and ecosystems. In recent years, ozone pollution in China has gradually become a prominent issue, especially in the North China Plain (NCP). To study the long-term spatio-temporal variation patterns of O3 in the NCP, this study selected 230 monitoring stations in the NCP from 2016 to 2020 as research objects, used the Kriging interpolation method and global Moran’s index to discuss the spatial-temporal distribution of O3, combining meteorological and social statistical data to analyze the causes underlying regional differences. The temporal analysis demonstrated that the O3-8h average concentrations increased annually from 2016 to 2018 and decreased from 2019 to 2020. The O3 concentrations were higher in spring and summer (117.89–154.20 μg/m3) and lower in autumn and winter (53.81–92.95 μg/m3). The spatial analysis revealed that O3 concentrations were low in the north and south of the NCP but high in the central area. The spatial distribution of O3 exhibited considerable cross-seasonal variability. Both meteorological conditions of high temperature and low pressure increased O3 concentrations. The spatial distribution of O3 varied depending on the period. However, the central and western regions of the Shandong Province were constantly characterized by high O3 concentrations. This pattern has been likely formed by heavy industry in the Shandong Province, as large-scale industrial production and frequent traffic flows produce a large amount of precursors, thereby exacerbating regional O3 pollution. These characteristics were attributed to emission reduction policies, meteorological conditions, the emission intensity of anthropogenic sources, and regional transport in the NCP. Overall, for cities with heavy industrial facilities in the central NCP, a timely adjustment of the energy and industrial structure, effectively controlling the emission of precursors, promoting new clean energy, and strengthening regional joint prevention and control are effective ways to alleviate O3 pollution.

Tubulin is an integral part of the cytoskeleton and plays a pivotal role in cellular signaling, maintenance, and division. β-tubulin is also the molecular target for taxane compounds such as docetaxel (DTX) and cabazitaxel (CTX), both first-line treatments for several solid cancers. Increased expression of Class III β-tubulin (TUBB3), a primarily neural isoform of β-tubulin, correlates with taxane resistance and poor prognosis. Although tyrosine kinase c-Src has been implicated to phosphorylate β-tubulins during both hematopoietic and neural differentiation, the mechanisms by which Src modulates tubulins functions are still poorly understood. Here, we report, for the first time, that TUBB3 is phosphorylated at Tyrosine 340 (Y340) by c-SRC in prostate cancer cells. We also showed that Y340 phosphorylation regulates TUBB3 protein stability and subcellular localization. Furthermore, we demonstrated that inhibition of SRC kinase activity compromises spindle stability in mitotic cells, at least partly due to the lack of TUBB3 Y340 phosphorylation. Given the importance of TUBB3 as a clinical biomarker of poor prognosis and drug resistance, characterization of TUBB3 posttranslational regulation could potentially serve as new biomarkers for disease recurrence and/or treatment failure.

The cyclin-dependent kinase inhibitor p27 (Kip1) is an important regulator of the G1/S checkpoint. It is degraded by the SCF-SKP2 complex in late G1 thereby allowing cells to progress to the S phase. Here we investigated the role of the E3 ubiquitin ligase RNF6 (Ring Finger Protein 6) in cell cycle progression in prostate cancer cells. Our data demonstrate that RNF6 can promote cell cycle progression by reducing the levels of p27. Knockdown of RNF6 led to an increase in the stability of p27 and to the arrest of cells in the G1 phase. RNF6 interacted with p27 via its KIL domain and this interaction was found to be phosphorylation independent. RNF6 enhanced ubiquitination and subsequent degradation of p27 in the early G0/G1 phase of the cell cycle. Knockdown of RNF6 expression by short hairpin RNA led to inhibition of the CDK2/Cyclin E complex thereby reducing phosphorylation of Retinoblastoma protein (Rb) and to a subsequent decrease in cell cycle progression and proliferation. Our data suggest that RNF6 acts as a negative regulator for p27kip1 leading to its proteasome-dependent degradation in the early G0/G1 phase of the cell cycle.

Background and Aims: The COVID-19 pandemic poses a great challenge to healthcare. We aimed to investigate the impact of COVID-19 on the healthcare of patients with inflammatory bowel disease (IBD) in epicenter and non-epicenter areas.Methods: Patients with IBD from Hubei province (the epicenter of COVID-19) and Guangdong province (a non-epicenter area), China were surveyed during the pandemic. The questionnaire included change of medications (steroids, immunomodulators, and biologics), procedures (lab tests, endoscopy, and elective surgery), and healthcare mode (standard healthcare vs. telemedicine) during 1 month before and after the outbreak of COVID-19.Results: In total, 324 IBD patients from Guangdong province (non-epicenter) and 149 from Hubei province (epicenter) completed the questionnaire with comparable demographic characteristics. Compared to patients in Guangdong province (non-epicenter), significantly more patients in Hubei (epicenter) had delayed lab tests/endoscopy procedures [61.1% (91/149) vs. 25.3% (82/324), p < 0.001], drug withdrawal [28.6% (43/149) vs. 9.3% (30/324), p < 0.001], delayed biologics infusions [60.4% (90/149) vs. 19.1% (62/324), p < 0.001], and postponed elective surgery [16.1% (24/149) vs. 3.7% (12/324), p < 0.001]. There was an increased use of telemedicine after the outbreak compared to before the outbreak in Hubei province [38.9% (58/149) vs. 15.4% (23/149), p < 0.001], while such a significant increase was not observed in Guangdong province [21.9% (71/324) vs. 18.8% (61/324), p = 0.38]. Approximately two-thirds of IBD patients from both sites agreed that telemedicine should be increasingly used in future medical care.Conclusions: Our patient-based survey study in a real-world setting showed that COVID-19 resulted in a great impact on the healthcare of patients with IBD, and such an impact was more obvious in the epicenter compared to the non-epicenter area of COVID-19. Telemedicine offers a good solution to counteract the challenges in an unprecedented situation such as COVID-19.

The combination therapy of thalidomide and azathioprine (AZA) offers an alternative in clinical practice for Crohn's disease (CD) patients experiencing a loss of response to AZA monotherapy. However, little is known about the efficacy and safety of this combination therapy for patients with CD. This was a retrospective study of 122 consecutive CD patients who lost response to AZA therapy and had switched to a combination therapy of thalidomide and AZA. The primary outcomes were clinical response and clinical remission rates at week 24. Patients who had an initial response to combination therapy were continued on the treatment for remission maintenance. The secondary outcomes were the proportion of clinical relapse throughout maintenance. The Kaplan–Meier method was used to calculate cumulative rates, and Cox regression analysis was used for multivariate analysis. During induction, 80.3% (98/122) patients achieved clinical response within a median duration of 6.5 weeks, (interquartile range, 4.3–8.1 weeks). The rate of clinical remission at 24 weeks was 70.5%. During follow-up, 22.4% (22/98) of the patients that were maintained on combination therapy experienced clinical relapse. The proportions of patients in remission status at 12, 24, and 36 months were 85.1, 78.3, and 70.1%, respectively. Multivariate analysis revealed C-reactive protein >10 mg/L at disease relapse on AZA monotherapy [adjusted hazard ratio (HR), 4.72; 95% CI, 1.19–18.75, P = 0.027] and 6-thioguanine nucleotides level ≥235 pmol/8 × 108 erythrocytes at AZA monotherapy (adjusted HR, 5.32; 95% CI, 1.40–20.14, P = 0.014) were associated with disease relapse on combination therapy. The endoscopic remission rate was 63.6%. Mucosal healing was achieved in 23.6% of the patients. Both Crohn's Disease Endoscopic Index of Severity (13.4 ± 4.92 vs. 6.12 ± 5.24, P < 0.001) and Rutgeerts scores (3.23 ± 0.73 vs. 1.77 ± 1.59, P = 0.003) were significantly decreased with the use of combination therapy. Adverse events occurred in 62 (50.8%) patients, but only 13 (10.7%) necessitated therapy discontinuation. Thalidomide combined with AZA was effective in inducing clinical remission and sustaining long-term steroid-free remission in CD patients who lost response to AZA monotherapy.

The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal–oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.

Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling.

Background: Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms. Methods: We fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days. Liver injuries and SirT1-PGC-1α-mitochondrial function were analyzed. In in vitro experiments, HepG2 cells (CYP2E1 over-expressing cells) were incubated with ethanol ± 0.5 mmol/L NR. Lipid accumulation and mitochondrial function were compared. SirT1 knockdown in HepG2 cells were further applied to confirm the role of SirT1 in the protection of NR on lipid accumulation. Results: We found that ethanol significantly decreased the expression and activity of hepatic SirT1 and induced abnormal expression of enzymes of lipid metabolism in mice. Both in vivo and in vitro experiments showed that NR activated SirT1 through increasing NAD+ levels, decreased oxidative stress, increased deacetylation of PGC-1α and mitochondrial function. In SirT1 knockdown HepG2 cells, NR lost its ability in enhancing mitochondrial function, and its protection against lipid accumulation induced by ethanol. Conclusions: NR can protect against ethanol induced liver injuries via replenishing NAD+, reducing oxidative stress, and activating SirT1-PGC-1α-mitochondrial biosynthesis. Our data indicate that SirT1 plays an important role in the protection of NR against lipid accumulation and mitochondrial dysfunctions induced by ethanol. Keywords: Alcoholic liver disease, NAD+, Nicotinamide Riboside, SirT1, Oxidative stress, Mitochondrial biosynthesis

The internet of things (IoT) is the network of physical devices,vehicles,home appliances and other items embedded with electronics,software,sensors,actuators and network connectivity which enable these objects to connect and exchange data.Every sensor node is a source of information.In the offered method,telecom network operators could analyze the network data and discover the abnormal situation of the IoT terminals,so as to ensure the normal use of the IoT terminals.A network behavior tag for the IoT terminals by analyzing the network data in the telecom network,and a real-time monitoring method for the IoT terminal network behavior were described.And take the wearable industry application for example,the analysis process of the internet of things network behavior was described.